Idiopathic Membranous nephropathy MedDRA version: 21.1 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 100000004857
Conditions
Interventions
Product Code: LNP023
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: iptacopan
Current Sponsor code: LNP023
Other descriptive name: LNP023 HYDROCHLORIDE SALT
Concentration unit: mg milligram(
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Female or male adult (=18 years) subjects at screening visit with a diagnosis of idiopathic (primary) MN confirmed by renal biopsy within 36 months prior to screening. A renal biopsy may be taken at any time during the run-in period to confirm the diagnosis of MN and facilitate subject eligibility, if the most recent biopsy was performed greater than 36 months prior to the screening visit. • Anti-PLA2R antibody titer of = 60 RU/mL at screening visit (based on the EuroImmun ELISA test) • Urine protein = 3.5 g/24h at run-in and baseline visits • =50% reduction in both anti-PLA2R level and 24h urine protein between first measurement at screening or run-in visit and baseline • Estimated GFR (using the CKD-EPI formula) = 30 mL/min per 1.73 m2 at screening visit • Receiving stable dose at the maximum recommended dose according to local guidelines or maximum tolerated dose of ACEi and/or ARB and/or statins and/or diuretics for at least 8 weeks prior to Day 1 • Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae (in accordance with local guidelines) at least 28 days prior to Day 1 and no longer than 5 years prior to Day 1 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: • Secondary causes of MN, e.g. systemic autoimmune diseases, solid or haematological malignancies, infections or chronic intake of drugs (e.g. gold salts, NSAIDs, penicillamines) • Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive of an alternative or additional diagnosis to primary idiopathic MN • Previous treatment with B-cell depleting or B-cell modifying agents such as, but not limited to rituximab, belimumab, daratumumab or bortezomib • Previous treatment with immunosuppressive agents such as cyclophosphamide, chlorambucil, mycophenolate mofetil (or equivalent), cyclosporine, tacrolimus or azathioprine within 90 days prior to Day 1. Low dose systemic corticosteroid therapy is permitted, though the subject should have been on stable dose equivalent to =10 mg prednisolone for at least 90 days prior to Day 1 • Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as clopidogrel within 7 days prior to Day 1 • Presence or suspicion (based on judgment of the investigator) of active infection within 30 days prior to Day 1, or history of severe recurrent bacterial infections
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to ascertain the efficacy, safety, tolerability and pharmacokinetics of LNP023 over a 24-week treatment period compared with rituximab in subjects with idiopathic membranous nephropathy (MN). The primary endpoint of the study will be the ratio between baseline Urine Protein Creatinine Ratio (UPCR) and UPCR at 24 weeks of treatment (from 24h urine collection). The study will target subjects with idiopathic MN at high risk of disease progression, on the basis of serum anti-PLA2R antibody titer and high-grade proteinuria.;Secondary Objective: - To assess the safety and tolerability of LNP023 - To assess the relationship between LNP023 systemic drug exposure and pharmacodynamics, mode-of-action markers and clinical efficacy - To assess the effect of LNP023 compared with rituximab on proteinuria remission and renal function - To assess the pharmacokinetics of LNP023 ;Primary end point(s): Ratio between baseline UPCR and UPCR at 24 weeks of treatment (from 24h urine collection);Timepoint(s) of evaluation of this end point: Baseline, Day 113 and Day 169 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ECG parameters, vital signs, safety laboratory data, physical exam and collection of AEs • Plasma levels of Bb and sC5b-9 • UPCR measured in first morning void • Non-compartmental parameters related to drug exposure • Proportion of subjects with a complete remission, defined as proteinuria =0.3 g/day at 24 weeks of treatment, derived from 24h urine collection • Proportion of subjects with a partial remission, defined as reduction of proteinuria from baseline =50% plus final UP = 3.5 g/24h but >0.3 g/24h at 24 weeks of treatment, derived from 24h urine collection. • Change in eGFR applying the Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) equation from baseline to 24 weeks of treatment • Plasma: non-compartmental parameters in plasma related to total parent drug, including, but not limited, to Tmax, Cmax, AUClast and AUCtau will be calculated for each dose level. • Urine: renal plasma clearance derived from 24h urine at week 16. ;Timepoint(s) of evaluation of this end point: • Baseline, Day 1, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 266, EOS. Collection of AEs is continuous. • Baseline, Day 15, Day 29, Day 57, Day 113, Day 169, Day 266, EOS • Baseline, Day 15, Day 29, Day 57, Day 85, Day 113, Day 169, Day 266, EOS • Baseline, Day 113 and Day 169 • Baseline, Day 113 and Day 169 • Baseline, Day 113 and Day 169 • Baseline, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141, Day 169, Day 266, EOS • Day 15, Day 29, Day 57, Day 113, Day 169 • Day 113 | — |
Countries
Argentina, China, Czechia, France, Germany, India, Netherlands, Russian Federation, Singapore, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma Services AG
Outcome results
None listed